Effect of PPAR-γ agonist pioglitazone on the prolifeiration of malignant nesothelionma cells induced by HMGB1
10.3760/cma.j.cn121094-20201102-00600
- VernacularTitle:PPAR-γ激动剂吡格列酮抑制炎症介质HMGB1对恶性间皮瘤细胞增殖活力的影响
- Author:
Yanbin WANG
1
;
Wei SHEN
;
Yihan GAN
;
Jin ZOU
;
Yu ZHANG
;
Lijin ZHU
;
Li JU
;
Zhaoqiang JIANG
;
Shibo YING
Author Information
1. 310013 杭州医学院
- Keywords:
Pioglitazone;
Malignant mesothelioma;
peroxisome proliferators-activated receptor-γ;
High mobility group box-1
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2021;39(9):641-647
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and mechanism of PPAR-γ agonist Pioglitazone (PGZ) on the proliferation of malignant mesothelioma (MM) cells.Methods:In December 2019, MM cell lines MSTO-211H and NCI-H2452 were incubated with different final concentrations of PGZ (0, 10, 50, 100, 150, and 200 μmol/L) for different periods of time (24 h, 48 h, and 72 h) , and then the cell proliferation level was detected by CCK8 assay. After given various final concentration of PGZ (0, 10, 50, 100, 150, 200 μmol/L) the for 72 hours, the changes of number and morphology of MM cells were observed under an inverted microscope. The expressions of PPAR-γ and HMGB1 mRNA were determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) after treatment of MM cells with PGZ of 0, 10, 50, 100 μmol/L for 72 h. The MM cells were treated with PGZ at concentration of 0, 100 μmol/L for 72 h, and the protein expressions of HMGB1 were examined using Western blotting and immunofluorescence; the protein expressions of Ki67 were assessed by immunohistochemistry.Results:The cell viability rate of MM cells was decreased after treated with PGZ ( P<0.05) . Cell number in PGZ-treated group was significantly less than that in control group and morphology changes were observed under light microscope. QRT-PCR results revealed significantly increased PPAR-γ mRNA expression in the PGZ-treated group compared to the control group ( P<0.05) . There was a significant decrease in the mRNA expression level of HMGB1 in the PGZ-treated group (100 μmol/L) as compared to the control group in MSTO-211H ( P<0.05) ; however, the expression level of HMGB1 in NCI-H2452 was an increase or no significant differences ( P>0.05) . Western blotting and immunofluorescence results showed that the protein expression of HMGB1 was reduced in the PGZ-treated group compared with the control group in MSTO-211H ( P<0.05) , but the protein expression of that in NCI-H2452 was no significant differences ( P>0.05) . Immunohistochemistry results showed increased expression of proliferation marker Ki-67. Conclusion:Pioglitazone suppresses the proliferation of MM cells through inhibition of HMGB1 by the activation of PPAR-γ.
